Interpretation of Troponin Values
Transcript of Interpretation of Troponin Values
Interpretation of Troponin Values
John Coyle, M.D.
February 9, 2005
Title Page
01. One cc of
Blood
1.67 Years.
(Really)
Kuida, H. Fundamental Principles Of Circulation Physiology For Physicians. Elsevier, 1979. p.20. 02. 1cc though 1 capillary
Cardiomyocyte
Troponin Overview
Antman EM, N Engl J Med 346: 2079 – 2082,
2002
03. Troponin Overview
04. RELATIVE SIZE OF MYOCARDIAL PROTEINS
Marker Size (kd) % Cytoplasmic
Myoglobin 18 100
Troponin I 24 2
Troponin T 33 6
CK/CK MB 86 100
AST 111 60
LDH 135 100
RELATIVE SIZE OF
MYOCARDIAL PROTEINS
Wu WHB et al. Clinical Chemistry 45: 1104–1121
(1999) 05. Cardiac Marker
Release
10
Siz
e o
f M
yo
card
ial
Infa
rcti
on
(g
ram
s)
0.01
100
0.001
1
0.1
ECHO CK,
AST
CK-
MB
TROPONINEKG
Head of a Pin
Normal heart weight = 230-340 grams, ~2x10^9 - 2x10^10 cells Dufour DR, AACC, Washington VA Medical Center
06. Marker Sensitivity
(gm)
Head of a pin = 0.0148 gm
The Original Data Portion of the Presentation
07. Head of a pin weight
“Currently available analyses demonstrate no threshold below which elevations of
troponins are harmless and without negative implications for prognosis. Thus, any other
definition of MI would involve an arbitrary setting of limits for an abnormal troponin and would
be open to criticism and considerable debate. It should be emphasized that there is continuity
from ‘minimal myocardial damage,’ characterized by elevation of cardiac troponin without
apparent elevation of other biomarkers (also termed ‘infarctlet’ or ‘necrosette’), to the classic
‘large myocardial infarction,’ often complicated by heart failure, shock or life-threatening
arrhythmia. In applying the proposed new diagnostic criteria to clinical practice, patients should
not be labeled primarily as “myocardial infarction” but rather as patients with coronary artery
disease with MI.”
08. MI Redefined
Pop Quiz:
As the physician on call, you are contacted by the night
Laboratory technician who relays a worrisome report. A
collection of 52 blood samples has arrived, marked “Study
Subjects”. Of these 52 samples, 32 show a troponin level
above normal, and 20 values are in the laboratory’s
“Myocardial Infarction” range.
At this point, you should probably
(a) Summon the EMSA Mega-Bus
(b) Expect a change in Homeland Security’s Color Level
(c) Call ESPN
09. Pop Quiz: Tpn Samples
Whyte G et al. Impact of marathon running on cardiac structure and function in recreational runners. Clinical Science (2005)
108: 73–80.
“Detectable increases in biomarkers of cardiac injury are indicative of injury to the myocardium, but
elevations are not synonymous with an ischemic mechanism of injury. Therefore, increases do not now
and did not in the past mandate a diagnosis of myocardial infarction.” Jaffe AS et
al. Circulation 102 (2000):1216-1220.
10. London
Marathon/Jaffe
Pop Quiz:
Which of the following test findings always represents an
emergency?
(a) Arterial Blood Gas showing pH = 6.91
(b) Venous blood sample showing Potassium = 9.1
(c) Arterial Blood Gas showing PO2 = 30
(d) EKG showing 5 mm of ST elevation in leads V1-V6, I and
aVL in a patient with ongoing chest pain
(e) Troponin = 0.10 ng/ml (Normal <0.07 ng/ml) in an
asymptomatic person
11. Pop Quiz: High Risks?
12. Higgins’ Tpn Title Page
Related to myocardial damage
•Acute coronary syndromes — myocardial
infarction and unstable angina
•Acute graft failure in cardiac transplant
patients
•Cardiac amyloidosis
•Cardiac contusion
•Cardioversion
•Cerebrovascular accident
•Chemotherapy
•Coronary vasospasm
•Heart failure, acute
•Heart failure, chronic, ischemic,
•Heart failure, nonischemic*
•Human immunodeficiency virus disease
•Implantable cardioverter defibrillator shocks
•Interventional closure of atrial septal defects
•Left Ventricular Hypertrophy
•Myocarditis
•Pericardial effusion
•Pericarditis
•Percutaneous coronary intervention
•Pulmonary embolism
•Postoperative, cardiac and noncardiac
surgery
•Radiofrequency ablation
•Scorpion envenomation, others
•Sepsis and septic shock
•Subarachnoid hemorrhage
•Tachycardia
•Ultraendurance exercise
(marathon,triathlon)
•Endocarditis
13. Troponin Causes: Part 1
Potential analytical causes
•Assay cross-reactivity
•Alkaline phosphatase, elevated
•Antibody crossreactivity
•Bilirubin, elevated
•Cirrhosis of liver
•Hemolysis
•Heterophile antibody
•Rheumatoid arthritis, rheumatoid factor
•Decreased clearance
•Renal failure, acute and chronic
Miscellaneous
•Central nervous system disorders
(including grand mal seizure)
•Hematologic malignant disease
•Labour and delivery
•Pre-eclampsia
•Perinatal hypoxia
•COPD exacerbation
•Pacemaker implantation
•Postpartum hemorrhage with shock
•Primary pulmonary hypertension
•Diabetic ketoacidosis
•Rhabdomyolysis
•Severe emotional stress
14. Troponin Causes: Part 2
15. Emotional Cardiomyopathy
Bucciarelli-Ducci C et al. Coronary Artery Disease 15:499-504, 2004. 16. Outcome: ER-Tpn-Cath
Chest Pain Patients: Risk of Various Troponin I Levels
Antman EM, N Engl J Med 346: 2079 – 2082, 2002 (Ref TIMI IIIB) 17. Risk of Tpn Levels
Dokainish H et al. J Am Coll Cardiol 2005;45:19 –24. Prognostic Implications of Elevated Troponin in Patients With Suspected Acute Coronary
Syndrome But No Critical Epicardial Coronary Disease (A TACTICS-TIMI 18 Sub-Study) 18. 6-mo. Outcome vs Tpn
19. Atherosclerotic Plaques Are Common
“With the appearance of the first luminal irregularity, at least 80% of the coronary tree is already arteriosclerotic.” Nissen,
JACC 41:106S, 2003
N = 262
Lesions by angio = 8%, by
IVUS = 52%
Atherosclerotic Plaques Are Common
20. What Category of Narrowing Produces the Greatest Hazard? Mild.
What Category of Narrowing Produces the Greatest Hazard?
Mild.
A 69 y.o. man, who had stroke at age 64 (left caudate nucleus), was admitted with prolonged
chest pain (6 hours) and dyspnea. The EKG showed atrial fibrillation with ventricular rate =
120 – 150 bpm. BP = 94/61. What were the coronary angiographic findings?
Nunes JP et al. Acta Cardiol 59:346-6, 2004. 21. A.Fib & RVR - Tpn
Normal.
22. Outcome of
#22
Pop Quiz:
At your child’s school’s “back to school” night, you are
approached by another parent who has received very
troubling news about her niece. The child, who is 8
years old, was admitted to the hospital with fever. The
next day, the child’s physician unexpectedly told her
parents that she had suffered a heart attack.
Your next move should be to
(a) Give sympathetic support
(b) Challenge the premise
(c) Give sympathetic support and silently challenge the
premise.
23. Pop Quiz: Peds & Tpn
Septic Shock in Children:
Troponin Values
Fenton KE et al. Pediatr Crit Care Med. 2004 Nov;5(6):533-538 (Children’s National Medical Center, Washington DC)
24. Peds Sepsis & Tpn 1
Troponin in Sepsis: Cell Death vs Cell Leak
Wu AH. Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible
myocardial depression? Intensive Care Med 2001;27:959-61. 25. Tpn: Cell Death vs
Leak
Sepsis in Children:
Troponin Values
26. Peds Sepsis & Tpn 2
Elevated Troponin in Children
Treated with Doxorubricin for
Acute Lymphocytic Leukemia
Lipshultz SE et al. The Effect of Dexrazoxane on
Myocardial Injuryin Doxorubicin-Treated Children
with Acute Lymphoblastic Leukemia.N Engl J Med
2004;351:145-53. (Univ.of Miami and collaborators)
27. Peds: Tpn & Chemo
Pop Quiz:
As the physician on call, you are contacted by the Surgery
Service to evaluate a patient in SICU. This 27 y.o. man was
involved in an automobile accident after his vehicle left the
road at an estimated speed of 105 mph. He was trapped in
the car for nearly 2 hours before being pried out by the Jaws
of Life. Reason for the consultation is troponin elevation.
After reviewing the chart, you should probably order
(a) An EKG
(b) An Echocardiogram
(c) A copy of the Guinness Book of World Records’ section on
blood alcohol levels
28. Pop Quiz: Rhabdo & Tpn
Troponin and Trauma
Troponin I assay: Limit of detection = 0.04ug/L, x>0.4ug/L =
significant myocardial injury, x>1.5ugm/L = threshold for
diagnosis of myocardial necrosis. In 5% of 86 pts. with elevated
troponin, CAD was felt to be at cause.
Edouard AE et al. Anesthesiology 101:1262-68, 2004.
29. Troponin and Trauma
Pop Quiz:
As the physician on call, you are asked to see a 23 y.o. man
who arrived in the E.R. after being dumped on the sidewalk
from a car that promptly sped away. The patient was
comatose, hypotensive and tested positive for heroin,
cocaine and methamphetamine. His elbows, sacrum and
heels were reddened. CPK was 9,000. Troponin I was
elevated, prompting consultation.
At this point, you should probably
(a) Intubate the patient and admit to the MICU
(b) Take steps to avoid renal damage
(c) Practice the “Just Say No” speech
30. Pop Quiz: Drug OD & Tpn
Punukollu G et al. International J of Cardiol 96 (2004): 35-40
Elevated Serum Cardiac Troponin I In Rhabdomyolysis
Elevated troponin >0.6 ng/ml
31. Rhabdo/Drugs & Tpn
Pop Quiz:
As a physician working in a heart failure clinic, you are
caring for a 30 y.o. man who has severe dilated
cardiomyopathy. He had coronary angiography (normal)
at the time of diagnosis 3 months ago. Due to a clerical
mix-up, a blood sample that was supposed to have been
sent for electrolyte determination instead was used for a
troponin measurement. Troponin I was slightly elevated.
Your next move should be to
(a) Contact the patient and admit to ICU
(b) Schedule another coronary angiogram
(c) Contact the patient, explain the test result, urge full
compliance and push for maximum medical therapy
32. Pop Quiz: CHF & Tpn
Troponin Elevation In Chronic Congestive Heart
Failure
Perna ER et al. Circulation. 2004;110:2376-2382.
33. CHF Chronic and Troponin
Troponin in CHF – ADHERE Registry
Peacock WF, Abstract 2004 Am. Coll Emergency Physicians 35. CHF-ADHERE-Troponin
Setsuta K, et al. Am J Cardiol 84:608-611,
1999.
Troponin Elevation In Acute Congestive Heart
Failure
36. CHF-Acute & Troponin 2
Severe congestive heart failure is associated with noncontiguous areas of myocardial
cell death, structural abnormalities in viable myocytes, and progressive interstitial
fibrosis, which lead to worsening heart failure through cardiac remodeling.We
theorize that the levels of cardiac troponin I in heart failure patients reflect cellular
injury and ongoing degradative processes of the contractile apparatus. These levels
are most likely part of the remodeling of the myocardium, and they sensitively
monitor the cell death that accompanies the spontaneous progression of heart failure.
The progressive impairment of cardiac structure and function occurs through a
number of putative processes that include neurohormonal factors, oxidative stress, and
a number of cytokines. Each of these factors can promote cardiac cell death by
producing either myocyte necrosis or myocyte apoptosis through activation of specific
genetic pathways. Both processes may be more common forms of myocardial cell
death than initially believed, because focal and diffuse loss of contractile units
constitutes the major structural characteristic of advanced heart failure and
conditions the progression of the disease.
Pathophysiology of Troponin-I Elevation In CHF Patients
Missove E, et al Circulation. 1997;96:2953-2958. (University Hospital of Montpellier, France)
37. Mechanism of Tpn in CHF
38. Definition:
Acute coronary syndrome (ACS) is a term that refers to the
entire spectrum of acute MI, including acute myocardial
infarction with and without ST-segment elevation and
unstable angina. The final classification of Q-wave or non-
Q-wave MI or unstable angina is a retrospective process that
is not possible for 24 hours or more after presentation.
Christopher B. Granger, M.D., FACC,
ACC ACS Module, 2004
Definition:
Pop Quiz:
At 6 pm you are called to the E.R. to evaluate an 82 y.o.
woman who has been transferred from an outlying
hospital for evaluation of chest pain that started one
hour earlier. Lab sent from the other hospital showed a
troponin level of 0. The patient continues to have chest
pain, and EKG shows 2-5 mm of ST elevation in 2, 3,
aVF, V5 and V6.
Your next move should be to
(a) Admit the patient to the ICU
(b) Get more enzyme results
(c) Take the patient directly to the Cath Lab
39. Pop Quiz: STEMI
40. STEMI – EKG - IMI
LVH LBBB Acute
Pericarditis
Hyper-
kalemia
Acute
ASMI
Acute
ASMI
Brugada
Syndrome
41. ST Elevation -
Causes
42. Time and Infarction Size
Time and Infarction Size
43. Time, Mortality and Infarction Size
Gersh BJ et al. JAMA. 2005;293:979-986
Time, Mortality and Infarction Size
44. Angioplasty vs.
Thrombolysis for
Acute ST-Elevation MI
Andersen HR, Nielsen TT, Rasmussen K, Thuesen L. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial
infarction (DANAMI-2). N Engl J Med. 2003;349:733-42
Angioplasty vs. Thrombolysis for
Acute ST-Elevation MI
Pop Quiz:
At 6 pm you admitted an 82 y.o. woman to a monitor bed
after 2 hours of chest discomfort, shortness of breath
and EKG showing non-specific ST-T abnormalities.
Following treatment in the E.R. she became symptom-
free. At 3am you are notified by the laboratory that her
troponin is 3.0 (normal <0.07). The patient is sleeping
peacefully. She is being treated with an ACS protocol.
Your next move should be to
(a) Move the patient to the ICU
(b) Make the patient NPO except for clear liquids, start low
dose I.V. fluids, avoid caffeine
(c) Obtain a 7:15 am Cardiology consult
45. Pop Quiz: NSTEMI – Cath?
46. EKG with ST depression
MI Options
1. Watchful waiting.
2. Myocardial perfusion scanning.
3. Coronary angiography with possible angioplasty.
47. NSTEMI Rx Options
ACC Round Table on Management of Acute Coronary
Syndrome, October 2004.
Moderator: Dolph Hutter, M.D., Professor of Medicine, Harvard
Deepak Bhatt M.D., Interventional Cardiologist, Cleveland Clinic Foundation
James Tcheng M.D., Interventional Cardiologist at Duke, Associate Professor of Medicine at Duke University
Medical Center
Glenn Levine M.D., Chief of Critical Care and Director of the Cath Lab at the Houston VA, Associate
Professor of Medicine at Baylor College of Medicine
DOLPH HUTTER, MD: And then would you call your referral hospital and say, "I've got this guy. I want to send him in."
GLENN N. LEVINE, MD: I would. Again, I don't think that, unless the patient is having active chest pain with dynamic ST
depressions in front of your eyes, in which case I would emergently take the person to the lab, I don't think we have data
that this person needs to be emergently taken to the lab.
DOLPH HUTTER, MD: Well, that's a good point.
GLENN N. LEVINE, MD: Versus, say, urgently taken to the lab.
DOLPH HUTTER, MD: All right. That's a good point. So if a guy comes in at two o'clock in the morning and he's got the
markers, but you put him on the programs, which we'll discuss subsequently, you say, "Look, let's get him in there. They can
take a look at him next morning." Is that reasonable? If he's stable?
GLENN N. LEVINE, MD: I think that's appropriate, and I don't think we have any data at this point that for a non-ST
elevation ACS patient who is not having active chest pain, that he needs to be emergently taken to the cath lab.
DEEPAK BHATT, MD: Yes, I think Glenn and Jimmy are right on the mark. Really, the bulk of data support an early invasive
strategy. Exactly how early, there is some ongoing investigation to see whether even earlier is better. But for right now, I'd
say in a stabilized patient within 48 hours or so is an appropriate time frame.
48. NSTEMI Roundtable
49. State Bird of Oklahoma?
State Bird of Oklahoma?
Report shows Costa Ricans live longer than Oklahomans NELLIE KELLY World Staff Writer, 02/20/2003
Planning a Lower-Risk America
Average Number of Cigarette Packs per Year per Capita
40
88
109
0
20
40
60
80
100
120
California U.S. Oklahoma
50. Smoking: OK vs US
Planning a Lower-Risk America
Oklahoma is the only state whose death rate has been increasing since 1990.
January 3, 2002: Fattest cities in the US. Number 11 = Tulsa 51. Oklahoma’s Poor Health
Summary
1. Troponin-measurement technology represents a remarkable advance in the
ability to gauge injury to myocardial cells.
2. The astonishing sensitivity of this technique, with abnormal results
beginning at a level of ~4-10 millionths of total heart mass, renders our
previous notions of the nature and significance of myocardial injury
obsolete.
3. Because of the extreme sensitivity of troponin in detecting heart injury,
careful usage of terms must be employed. It is suggested that the
designation “myocardial infarction” be limited to non-micro ischemic
myocardial damage. Troponin elevation due to non-ischemic causes should
probably be called “[statement of magnitude] myocardial injury due to
[nature of process].”
4. Troponin elevations in a variety of illnesses have illuminated aspects of
pathophysiology that were previously unsuspected.
5. Clinical response to any lab test result must be guided by the context
framing the test. This principle applies emphatically in the case of troponin
measurement. 52. Lecture Summary
53. Sunset? Green Ray
54. Galileo
Probe Photo
Endothelial EROSION with a Small
Thrombus
“In clinical trials, about 20% of ACS patients undergoing early angiography exhibit no hemodynamically significant
stenosis.” Nissen, JACC 41, 206S, 2003
Plaque RUPTURE Causing Major
Thrombosis
Micro-Emboli and ACS